The quinolones, oxolinic acid (OXO), flumequine (FLU), and nalidixic acid (NAL), are antibacterial drugs effective against Gram-negative bacteria. Quinolones are used in both human and veterinary medicine, but are currently not approved by the U.S. Food and Drug Administration for use in food fish. A liquid chromatography-fluorescence (LC-FL) method was developed to determine OXO, FLU, and NAL residues in shrimp. An additional liquid chromatography–mass spectrometry (LC–MS n ) method was created to confirm these residues using the same sample extract. Samples were prepared with a simple ethyl acetate extraction followed by solvent exchange into 0.2% formic acid and cleaned-up with hexane. Reverse phase chromatography was used to separate the three compounds in both procedures. For the LC-FL determinative method, fluorescence emission was monitored at 369nm with excitation at 327nm. With electrospray ionization, the three most abundant ions from the MS 3 product ion spectrum were used to identify OXO, FLU, and NAL in the confirmation procedure. Shrimp samples fortified at levels ranging from 7.5 to 100ngg −1 were used to validate both methods.